Exosomal MicroRNAs as Minimal Residual Disease Biomarker Candidates in Childhood Acute Lymphoblastic Leukemia

Context Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Five-year survival rate is nearly 90%. Measurement of minimal residual disease (MRD) at set time points has become a fundamental part of stratified treatment in ALL. Treatment response is assessed using bone marrow samples. Exosomal microRNAs are putative biomarkers in many malignancies. In childhood leukemia, the potential of exosomal microRNAs as biomarker candidates has not established yet. Objectives The aim of this study was to evaluate exosomal microRNAs in peripheral blood and associated with flow cytometry (FC) MRD in childhood ALL. Design and settings Exosomal fractions of 52 platelet-free plasma samples were obtained from 13 newly diagnosed de novo ALL patients and 6 healthy controls by ultracentrifugation. RNA isolation was carried out using miRNeasy Serum/Plasma Kit (Qiagen). Quantitative real-time PCR was carried out using TaqMan advanced qPCR methodology. Results The expression of the tested microRNAs in exosomal fraction as well as in platelet-free fraction correlated in diagnostic samples but not any other sampling times during the induction therapy. Significant decrease was observed in both miRs between the day of diagnosis and day 15 of induction therapy. Expression changes in one of the tested exosomal microRNAs correlated in every given time point with day 15 FC MRD (p Conclusion Based on our results, certain exosomal microRNAs\u0027 expression changes seem to be a better biomarker candidate than circulating microRNAs detected in platelet-free plasma of de novo childhood ALL.